Enhancement of Breast Cancer Therapy by 6-Aminonicotinamide
Final rept. 6 Apr 1998-5 Apr 2002
SLOAN-KETTERING INST FOR CANCER RESEARCH NEW YORK
Pagination or Media Count:
This work was undertaken to determine if 6-aminonicotiamide 6AN can enhance efficacy of radiation XRT andor chemotherapy paclitaxel or adriamycin. The study was done in hormone resistant MDA-MB-435 and hormone sensitive MCF-7 breast tumors. The interval between 6AN and XRTchemotherapy was determined by 31P NMR spectral changes. Spectral changes were noted post 6AN in perfused MCF-7 and MDA-MB-435 cells including a decrease in the ratio of phosphocreatine to inorganic phosphate Pi and an increase in 6-phosphogluconate a product of the pentose phosphate pathway to Pi. Similar changes were noted in vivo in the MCF-7. 6AN enhanced the effect of XRT 2 Gy and adriamycin in the MCF-7 but inhibited the effect of paclitaxel. In the MDA-MP-435, no enhancement was noted in vitro. In vivo, 6AN enhanced the effect of radiation 5Gyfraction and adriamycin in the MCF-7. Treatment with paclitaxel was too toxic with SAN to evaluate. In the MDA-MB-435, enhancement of XRT was noted with 6AN, but not of adriamycin. The latter may have been to a lower dose of adriamycin 5mgkg than was used in the MCF-7. 6AN inhibited paclitaxel in the MDA-MB-435. 6AN was effective at non-toxic doses in enhancing the effect of XPT in both MCP-7 and MDA-MB-435, but inhibited paclitaxel in the latter tumors.
- Medicine and Medical Research